Sexually. Management Guidelines Published by

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Sexually

TranSmiTTed

infecTionS

management Guidelines

2013

Published by

DSC CLINIC

NATIONAL SKIN CENTRE

© 2013

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PREFACE

The DSC STI Management Guidelines are designed to serve as a concise and comprehensive reference manual for doctors, paramedical personnel, medical students and counsellors. This 6th_{edition contains updates in all chapters.}

Once again, there are key references for each chapter, using the latest available evidence. In particular, this edition includes updates on issues of antimicrobial resistance in gonorrhoea. There is worldwide concern about decreasing sensitivity to parenteral cephalosporins and in 2012, the British and European authorities have already recommended using a higher dose of intramuscular ceftriaxone, administered together with a night dose of azithromycin, regardless of presence of Chlamydia co-infection. It is hoped that this would delay the development of resistance in the gonococcus. Locally we continue to monitor the trends of antimicrobial resistance in Neisseria gonorrhoeae.

There is also a new chapter on vaccinations and the prevention of STIs. Most notably, since the last edition, vaccines that are effective against HPV infection have become widely available. The chapter on HIV infection has been updated to provide the latest information on HIV management and therapeutic regimens. The chapter on non-occupational post exposure prophylaxis against HIV infection has been expanded. We have also added a new table to the annex summarizing the common laboratory tests that are used in screening for STIs. We hope you will find this book useful and welcome feedback and suggestions on ways to improve it. We would like to thank our co-authors for their valuable contributions, and the staff at DSC clinic for their continued support and excellent work.

Joint Editors Contributors Dr Tan Hiok Hee Prof Roy Chan Dr Priya Sen Dr Martin Chio Dr Ellen Chan Dr Gavin Ong Ms Amy Chan

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PRINCIPLES OF STI MANAGEMENT

1. TAKING A HISTORY

It is easier to start history taking with questions relating to the medical complaint. For male patients, presenting symptoms are urethral discharge, dysuria, ano-genital sores, rashes or growths. Female symptoms include vaginal discharge, dysuria, anogenital ulcers, rashes or growths. Throat and rectal infections are usually asymptomatic.

The sexual history of a patient with or suspected to have a STI/HIV should include information on:

• Recent sexual exposures – usually the last and second last partner, spouse, casual or regular partner, or sex worker, gender, whether local or overseas

• Type of sexual exposure - vaginal, anal or oral

• Use of condoms – for vaginal, anal, oral sex

• Use of other contraceptives

• Previous STI

It should be noted that a reliable history is only possible in a setting of privacy, confidentiality and if the healthcare provider has a non-judgmental attitude.

Other relevant medical information should include:

• Prior treatment, including traditional medications

• Self medication

• Drug allergies

• Menstrual, gynaecologic and obstetric history in females

After an accurate history is obtained you will be able to ascertain the patient’s risk of contracting a STI/HIV and to order the relevant laboratory investigations.

2. PHYSICAL EXAMINATION

The anogenital and inguinal regions should be exposed and carefully examined in good lighting. Males can be examined lying on the examination couch (preferred) or standing up. Females should be examined in the lithotomy position. Proctoscopic examination should be performed on males and females who practice anal intercourse. If indicated, a general examination should be performed when there is the suspicion of syphilis, Reiter’s disease, disseminated gonococcal infection and HIV infection.

3. LABORATORY INVESTIGATIONS

The correct use of laboratory tests in STI includes:

• Obtaining adequate specimens for direct smears, cultures and other detection methods e.g. molecular detection.

• Ordering the appropriate blood tests.

• Proper storage and transport of the specimens.

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Tests of little or doubtful value should not be performed; these include serology tests for chlamydia and gonorrhoea, and non type specific serological tests for herpes simplex virus. There are increasing examples of point-of-care rapid tests for HIV, syphilis, chlamydia and gonorrhoea. While convenient they need to be used only when their performance has been adequately evaluated. Rapid tests for HIV and syphilis are generally accurate; those for chlamydia and gonorrhoea are not as accurate.

4. MAKING A DIAGNOSIS Accurate diagnosis is based on:

• A good history

• A thorough physical examination and

• Performing appropriate laboratory tests

History and physical examination are often the basis of reaching a diagnosis in primary healthcare settings like general practitioners’ clinics. Making an aetiological diagnosis is usually possible in referral centres and hospitals with adequate laboratory backup.

It must be remembered that clinical syndromes (e.g. urethritis and genital ulcer disease) may be polymicrobial in aetiology. All patients with a STI should be screened for other infections; in particular they should be offered tests for syphilis and HIV infection.

5. TREATMENT

Treatment regimens must be efficacious, safe, easy to comply with, affordable, preferably given in a single dose, easily administered; and it should be provided as far as possible on the patient’s first visit.

Treatment is thus often based on clinical diagnosis only e.g. urethral discharge, vaginal discharge, and genital ulcers. It is often not possible to have an aetiological diagnosis at the first visit. In these situations it is important to ensure that the medications used are effective against all the major pathogens that may be causes of the syndrome. Wherever possible an aetiological diagnosis should be confirmed by laboratory tests. Approaches to making a clinical diagnosis are provided in annexes III, IV and V.

6. COUNSELLING

a) Prevention of disease transmission

All patients should be informed of the diagnosis, nature of treatment and expected outcome, the need to comply with and complete the treatment, reporting of side effects, and avoidance of sex until cured. In some cases follow-up for tests-of-cure may be necessary.

b) Prevention of further infection

Counselling skills which include respect for privacy, compassion and a non-judgemental attitude are essential for effective delivery of prevention messages.

All patients should be counselled on the methods of reducing their risk of acquiring a STI/ HIV in future, including abstinence, reducing the number of sexual partners (especially concurrency) and avoiding sexual contact with persons who have multiple sexual partners.

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They should be instructed on the correct and consistent use of condoms for vaginal, anal and oral sex. The following recommendations ensure the proper use of male condoms:

• Use a new condom with each sex act (e.g., oral, vaginal, and anal).

• Carefully handle the condom to avoid damaging it with fingernails, teeth, or other sharp objects.

• Put the condom on after the penis is erect and before any genital, oral, or anal contact with the partner.

• Use only water-based or silicone based lubricants with latex condoms. Oil-based lubricants (e.g. vaseline, massage oils, body lotions and creams) can weaken latex.

• Ensure adequate lubrication during vaginal and anal sex, which might require the use of exogenous water-based lubricants.

• To prevent the condom from slipping off, hold the condom firmly against the base of the penis during withdrawal, and withdraw while the penis is still erect.

They should be advised to seek medical attention if they feel that they have been exposed to an infection e.g. if the condom broke or slipped off.

They should not self-medicate or seek treatment from unqualified persons.

Repeaters (patients with multiple episodes of STI) should receive intensive counselling on strategies to reduce risk.

7. NOTIFICATION OF INFECTIONS

Certain STI are notifiable in Singapore. Reporting of STI and HIV/AIDS allows for accurate monitoring of disease trends; and is needed for monitoring and evaluating the National STI and AIDS control programmes.

Except for HIV/AIDS, there is no need to include the name, identity card number or address of the patient when notifying a STI; only demographic data (age, gender, ethnicity, nationality) for epidemiologic analysis is required. Notification of STIs is not meant for case detection or contact tracing. As such patient privacy and confidentiality is maintained.

Gonorrhoea, Chlamydia infection, syphilis (infectious, non-infectious and congenital), NGU, anogenital herpes (first episode and recurrent) should be notified to the DSC Clinic by fax (6299 4335) using form MD 131 or electronically https://www.cdlens.moh.gov.sg/cdlens/ within 72 hours of diagnosis.

HIV infection and AIDS should be notified to NPHU by fax (6254 1616) using form MD 131 or electronically - https://www.cdlens.moh.gov.sg/cdlens/ within 72 hours of diagnosis.

Viral Hepatitis (A, B, C) infections should be notified to CDD, MOH by fax (6734 8287 or 67319368) using form MD131 or electronically - https://www.cdlens.moh.gov.sg/cdlens/ within 72 hours of diagnosis.

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8. PARTNER NOTIFICATION / CONTACT TRACING

The public health objectives of partner notification are – to interrupt the transmission of the STI, identify populations at risk, reduce the incidence of infection; individual’s objectives are – to identify people who may benefit from treatment and counselling, provide individual counselling, and to prevent complications.

Partner notification can be undertaken either by the health care worker (provider referral) using telephone, letter or home visit; by the patient (patient referral); or a combination of the two (conditional referral). Maintaining the confidentiality of the index patient is paramount to successful contact tracing.

Patient delivered partner therapy (PDPT) refers to the practice of providing antibiotic treatment to the index patient to give to their partners is becoming popular in some places, and may become a strategy to control STIs in future.

9. CHEMOPROPHYLAXIS

Blind treatment of a STI in asymptomatic persons must be avoided. There is no universally effective antimicrobial. Furthermore chemoprophylaxis may suppress but not cure a STI. This may lead to complications, promote development of resistant strains of microbes, give a false sense of security to the patient and lead to onward transmission of infection. 10. EPIDEMIOLOGIC TREATMENT

Treatment of sexual contacts of patients (with a confirmed STI) without first obtaining laboratory confirmation may be indicated in situations where the risks of complications are high (e.g. in pregnancy), or when the follow-up of the contact may not be guaranteed or possible. Recommended treatment regimes must be used in these situations.

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BACTERIAL VAGINOSIS

DEFINITION

Bacterial vaginosis (BV) is a condition resulting from replacement of the normal H_2O 2-producing Lactobacillus sp. in the vagina with high concentrations of anaerobic bacteria (e.g. Prevotella species, Mobiluncus species, Gardnerella vaginalis, Ureaplasma and Mycoplasma hominis) leading to an increase in pH from less than 4.5 to as high as 7.0. It can arise and remit spontaneously in sexually active and non-sexually active women. The exact role of sexual transmission in the pathogenesis of BV is unclear.

CLINICAL FEATURES

BV may be asymptomatic or present with a fishy-smelling, thin homogenous vaginal discharge.

Risk factors include:

• Vaginal douching

• Receptive cunnilingus

• Recent change of sex partner

• Smoking

• Presence of STI LABORATORY TESTS

3 out of 4 of the following criteria should be present (Amsel criteria)

• Thin homogenous vaginal discharge that coats the vaginal wall and vestibule

• pH of vaginal fluid > 4.5

• Positive amine (fish-like) odour test (“whiff test”) before or after addition of 10% KOH

• Presence of clue cells on microscopy of vaginal discharge Note:

• Menses, semen, cervical secretions or douching may affect the pH

• A weakly positive “whiff test” may be produced by menstrual blood or semen

• Exclude trichomoniasis

Culture of G. vaginalis is not recommended because it can be cultured from the vagina of > 50% of uninfected women.

An alternative test involves use of a gram stained vaginal smear evaluated with the Hay/Ison criteria or the Nugent criteria.

Commercially available tests which perform adequately when assessed against Amsel and Gram stain criteria include:

• OSOM BVBlue which measures sialidase levels

• A prolineaminopeptidase test card (Pip activity TestCard)

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COMPLICATIONS

BV has been associated with adverse pregnancy outcomes (e.g. premature rupture of membranes, chorioamnionitis, preterm labour and preterm birth). BV is also associated with endometritis, PID and vaginal cuff cellulitis after invasive procedures (e.g. uterine curettage, hysterectomy, endometrial biopsy).

There is increasing evidence that the presence of BV (or absence of vaginal lactobacilli) has been shown to increase a woman’s risk of acquiring HIV, N. gonorrhoeae. C. trachomatis and HSV-2 via heterosexual intercourse.

TREATMENT

Indications for treatment:

1) All symptomatic women, pregnant or non pregnant [A]

2) Asymptomatic pregnant women with high risk for preterm delivery [A] 3) Asymptomatic women before surgical abortion procedures [A]

4) Women who do not volunteer symptoms may elect to take treatment if offered. They may report a beneficial change in their discharge following treatment

General Measures

Patients should be asked to avoid vaginal douching, use of shower gels, antiseptic agents or shampoos in the bath [C].

Recommended regimens

Metronidazole 400-500mg orally bid x 5-7 days [1a, A] or

Metronidazole 2g single dose [1b, A] or

Clindamycin cream 2% one full applicator (5g) intravaginally at bedtime x 7 days [1b, A] or

Metronidazole gel 0.75% one full applicator (5g) intravaginally once a day x 5 days [1b, A] Alternative regimens

Clindamycin 300 mg orally bid x 7 days [1b, A] or

Tinidazole 2g orally single dose [1b, A] Note:

• Metronidazole 2g single dose therapy may be slightly less effective at 4 week follow up [Ib].

• Patients should avoid consuming alcohol during treatment with metronidazole and for 24 hours thereafter.

• Clindamycin cream is oil-based and might weaken latex condoms and diaphragms.

• Non-antibiotic based treatment with probiotic lactobacilli or lactic acid preparations have not yielded consistently reproducible evidence of efficacy as treatments for BV and no recommendation on their use can be made at present.

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BV in Pregnancy Recommended regimens

Metronidazole 400-500mg orally bid x 7 days [1b, A] or

Metronidazole 200mg orally tid x 7 days [1b, A] or

Clindamycin 300 mg bid orally x 7 days [1b, A] Note:

• Intravaginal clindamycin cream administered at 16-32 weeks gestation has been associated with an increase in adverse events (e.g. low birthweight and neonatal infections). Therefore intravaginal clindamycin cream should only be used during the first half of pregnancy.

• Data is conflicting regarding the usefulness of screening and treating low risk asymptomatic pregnant women. Metronidazole use in the first trimester of pregnancy has not been shown to be teratogenic or mutagenic [Ia]

• Metronidazole enters breast milk and may affect its taste. The manufacturers recommend avoiding high doses if breastfeeding. Small amounts of clindamycin enter breast milk, therefore use an intravaginal treatment for lactating women [C]

• Screening for and treating BV in patients undergoing a termination of pregnancy reduces the incidence of subsequent endometritis and PID [Ia]

BV in HIV infection

BV tends to recur with a higher frequency in HIV-positive women. These patients should be treated with the same treatment regimens as for HIV-negative women.

Recurrent BV

There are few published studies evaluating the optimal approach to women with frequent recurrences of BV. Two studies reported a high incidence of BV in female partners of lesbians with BV [II].

Possible approaches are:

• Suppressive therapy: Metronidazole gel 0.75% twice weekly for 4-6 months [Ia]

• Metronidazole 400mg orally bid for 3 days at the start and end of menstruation (combined with fluconazole 150mg as a single dose if there is a history of candidiasis also) [Ia]

• Maintenance therapy involving acetic acid vaginal gel use at the time of menstruation and following unprotected sexual intercourse [III].

• Small studies using live yoghurt or Lactobacillus acidophilus have not demonstrated benefit [IIa]

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FOLLOW-UP

Follow-up is not necessary if symptoms resolve.

For high-risk pregnant women, a one month follow-up visit is recommended to evaluate if treatment is successful. Alternative regimens can be given for recurrent disease.

Long term maintenance regimens are not recommended. MANAGEMENT OF SEXUAL CONTACTS

No clinical counterpart is recognised in males and screening and treatment has not shown to be beneficial for the patient or the male partner. Although studies have reported a high incidence of BV in female partners of lesbian women with BV [II], no studies have as yet investigated the value of treating partners of lesbian women simultaneously.

References:

1. Cohen, C.R., et al. (1995). Bacterial Vaginosis and HIV Seroprevalence Among Female Sex Workers in Chiang Mai, Thailand. AIDS, 9:1093.

2. Ison, C. A. & Hay, P.E. (2002). Validation of a Simplified Grading of Gram Stained Vaginal Smears for Use in Genitourinary Medicine Clinics. Sex Transm Infect, 78(6), 413-415.

3. Joesoef, M.R., Hillier, S.L., Wiknjosastro, G., et al. (1995). Intravaginal Clindamycin Treatment for Bacterial Vaginosis: Effects on Preterm Delivery and Low Birth Weight. Am J Obstet Gynecol, 173:1527-1531.

4. Nugent, R.P., Krohn, M.A., & Hillier, S.L. (1991). Reliability of Diagnosing Bacterial Vaginosis is Improved by a Standardized Method of Gram Stain Preparation. J Clin Microbiol, 29(2), 297-301.

5. BASHH 2010). National Guideline for the Management of Bacteria Vaginosis. Retrieved from http://www.bashh.org/documents/62/62.pdf

6. Wilson, J.D., Shann, S.M., Brady, S.K., et al. Recurrent Bacterial Vaginosis: The Use of Maintenance Acidic Vaginal Gel Following Treatment. Int J STD AIDS, 16:736-738. 7. Workowski, K. & Berman, S. (2010). CDC Sexually Transmitted Disease Treatment

Guidelines (2010). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/ rr5912a1.htm

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CANDIDIASIS

DEFINITION

Genital candidiasis is the infection of the vulva, vagina, prepuce and glans penis by Candida albicans (80-92%) or occasionally by other Candida species (glabrata, tropicalis, krusei, parapsilosis), Torulopsis species, or other yeasts. It is not generally considered a sexually transmitted infection.

Female patients complain of vulval pruritus and discharge. Non-specific symptoms include soreness, burning, dyspareunia and external dysuria. Male patients may complain of a penile rash. Examination reveals vulval erythema, fissuring, satellite lesions, and thick curdy discharge in females; or white or red patches on the glans penis in males.

Predisposing factors include diabetes mellitus, use of long term oral antibiotics, steroid and oral contraceptives.

LABORATORY TESTS

• Gram-stain or wet mount (saline or 10% KOH) of swabs from the vulva/vaginal wall, or penis/prepuce will reveal budding yeast cells and pseudohyphae (sensitivity 60%)

• Vaginal pH 4 – 4.5

• Culture on Sabouraud media (isolation in the absence of symptoms and negative direct smear is not an indication for treatment)

• Serum antibodies should not be used for diagnosis DIAGNOSIS

Symptoms and signs of vulvo-vaginitis or balano-posthitis PLUS

Demonstration of yeasts/pseudohyphae on wet mount or Gram-stain or positive culture TREATMENT

Treatment is indicated for symptomatic patients. It is not recommended for asymptomatic patients with a positive Gram stain or culture because 10-20% of women harbour Candida species or other yeasts in the vagina in the absence of symptoms.

General advice

Vulval emollients and or topical antifungal/steroid creams may provide symptomatic relief for secondary associated vulval dermatitis. Avoid local irritants (e.g. perfumed products) and tight fitting clothing (IV, C).

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Recommended Regimens

Uncomplicated vulvovaginal candidiasis (VVC)

1. Clotrimazole vaginal pessary 200mg daily x 3 days or 500 mg single dose [II, A] or

2. Miconazole nitrate vaginal pessary 200mg daily x 3 days [II, A] or

3. Econazole nitrate pessary 150mg intravaginally nightly x 3 days [II, A] or

4. Nystatin pessary 100,000 U daily x 7 to 14 days [II, A] or

5. Butoconazole 2% cream 5g intravaginally x 1 day [II, A] or

6. Fluconazole 150mg orally single dose [II, A] Alternative Regimens

1. Clotrimazole pessary 100mg or cream (1%) 5g intravaginally daily x 7 days [II, A] or

2. Miconazole nitrate vaginal pessary 100mg or cream (2%) 5g intravaginally daily x 7 days [II, A]

or

3. Tioconazole ointment (6.5%) intravaginally 4.6g in a single application [II, A] or

4. Miconazole 1,200mg vaginal pessary x 1 day [II, A]

Note: The topically applied azole drugs are more effective than nystatin. Candidiasis in pregnancy

Only topical azole therapy should be given. Longer courses may be necessary. Oral azole therapy is contraindicated [II, B].

Candidiasis in HIV infection

Candidiasis tends to occur with a higher frequency and persistence in HIV-positive women and colonization rates correlate with the severity of immunosuppression. These patients should be treated with the same treatment regimens as for HIV-negative women.

Recurrent vulvovaginal candidiasis

This is defined as 4 or more episodes of symptomatic vulvovaginal candidiasis annually. Patients must be evaluated for any predisposing factors e.g. uncontrolled diabetes mellitus, immunosuppression, corticosteroid and long-term antibiotic use. Repeated courses of treatment may be required. Infection by less susceptible yeasts e.g. C glabrata may require a longer duration of therapy.

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Induction Regimens

1. Itraconazole 100mg orally bid x 1-3 days [II, A] or

2. Fluconazole 150mg orally single dose [II, A] Maintenance Regimens

1. Fluconazole 100-200mg orally once a week x 6 months [II, B] or

2. Clotrimazole pessary 500mg once a week x 6 months [II, B] or

3. Itraconazole 400mg once a month x 6 months [II, B]

Caution: Anecdotal reports of oral contraceptive failure with prolonged oral azole therapy. The creams and suppositories are oil-based and may weaken latex condoms and diaphragms. Risk of idiosyncratic drug-induced hepatitis with itraconazole.

MANAGEMENT OF SEXUAL CONTACTS

There is no evidence to support the screening or treatment of asymptomatic male sexual partners. For symptomatic balano-posthitis, topical imidazole creams bid x 7 days will usually eradicate the infection.

References:

1. BASHH (2010). National Guideline for the Management of Vulvovaginal Candiadisis. Retrieved Nov 1, 2011, from http://www.bashh.org/documents/50/50.pdf

2. Workowski, K. & Berman, S. (2010). CDC Sexually Transmitted Disease Treatment Guidelines (2010). Retrieved Nov 1, 2011, from http://www.cdc.gov/mmwr/preview/ mmwrhtml/rr5912a1.htm

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CHANCROID

DEFINITION

Chancroid is a sexually transmitted infection caused by the bacterium Haemophilus ducreyi. This infection is uncommon in Singapore, but still common in parts of India and South East Asia. Patients infected may have a co-infection with syphilis or herpes.

Infection with H. ducreyi may present with an erythematous papule that rapidly progresses into a pustule, which erodes into an ulcer. Infected persons may have more than one ulcer, and the lesions are almost always confined to the genital area and its draining lymph nodes. A typical chancroid ulcer is about 1 to 2 cm in diameter, but the size is variable, especially in HIV-infected patients. The ulcer is painful and has an erythematous base; the borders are clearly demarcated and sometimes undermined. The base of the ulcer is usually covered with a grey or yellow purulent exudate and bleeds when scraped.

The most common sites for chancroid are the prepuce, corona, or glans penis in men, and the labia, vaginal introitus, and perianal areas in women. Some cases of chancroid may go undiagnosed, especially in asymptomatic women with vaginal or cervical lesions.

The involved nodes may undergo liquefaction and present as fluctuant buboes. Most buboes arise one to two weeks after the appearance of the primary ulcer and are often quite painful. Untreated buboes may spontaneously rupture and discharge frank pus. Scarring may result despite successful therapy.

• Direct microscopy of a smear from ulcer showing Gram-negative coccobacilli (arranged in “shoals of fish” pattern) (poor sensitivity)

• Culture for H. ducreyi of a smear from ulcer or aspirate from buboes (sensitivity <80%)

• Diagnosis is often based on a typical clinical presentation and after exclusion of syphilis and HSV infection

• Multiplex PCR detection (>95%) TREATMENT

LOCAL TREATMENT

• Saline wash

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SYSTEMIC TREATMENT Recommended regimens

1. Ceftriaxone 250 mg i/m single dose [lb, B] or

2. Azithromycin 1 g orally single dose [lb, A] Alternative regimens

1. Ciprofloxacin 500 mg orally bid x 3 days [lb, B] or

2. Erythromycin base or stearate 500 mg orally qid x 7 days [Ib, B] or

3. Co-trimoxazole (trimethoprim/sulfamethoxazole) 160/800 mg (2 tabs) orally bid x 7 days Not recommended

Tetracyclines and Ampicillin

Other Management Considerations

Patients who are uncircumcised and patients with HIV infection do not respond as well to treatment as those who are circumcised or HIV-negative. Patients should be tested for HIV infection at the time chancroid is diagnosed. Patients should be retested for syphilis and HIV 3 months after the diagnosis of chancroid if the initial test results were negative.

FOLLOW-UP

Chancroid ulcers usually begin to heal within 3 days of treatment and should heal completely by 7-14 days. Inguinal lymphadenopathy will take a longer time to resolve. If there is no improvement by 7 days, the patient should be re-evaluated for:

• Compliance with medication

• Co-infection with another STI

• Co-infection with HIV

• Non-STI ulcer disease

• Resistant organism

The response of chancroid-associated lymphadenitis may occur more slowly. In one study, for example, 8 of 35 patients with inguinal lymphadenitis developed fluctuance that required needle aspiration despite successful treatment of the genital ulcer with erythromycin. In advanced cases, scarring may result despite eradication of infection.

Sex partners should be screened and treated when indicated if they had sexual contact with the patient 10 days before patient’s onset of symptoms.

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Special considerations Pregnancy

Ciprofloxacin is contraindicated during pregnancy and lactation. No adverse effects of chancroid on pregnancy outcome have been reported so far.

HIV Infection

HIV-infected patients who have chancroid should be monitored closely because, as a group, these patients are more likely to experience treatment failure and to have ulcers that heal more slowly. HIV-infected patients may require longer courses of therapy than those recommended for HIV-negative patients, and treatment failures can occur with any regimen. References:

1. Workowski, K. & Berman, S. (2010). CDC Sexually Transmitted Disease Treatment Guidelines. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5912a1.htm 2. BASHH. (2007). National Guideline for Management of Chancroid. Retrieved from

http://www.bashh.org/documents/85/85.pdf

3. WHO. (2003). Guidelines for the Management of Sexually Transmitted Infections. Retrieved from http://whqlibdoc.who.int/publications/2003/9241546263.pdf

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CHLAMYDIA TRACHOMATIS INFECTIONS

DEFINITION

Chlamydia trachomatis is a bacteria which can cause a variety of genito-urinary infections, depending on the serotypes. Chlamydial genital infections occur frequently among sexually active adolescents and young adults.

Serotypes D to K cause non-gonococcal urethritis, mucopurulent cervicitis, proctitis, epididymitis, pneumonia and conjunctivitis in the newborn. Lymphogranuloma venereum (LGV) is caused by serotypes L1-L3 (see section on LGV). Many adult genital infections and most rectal and pharyngeal infections caused by chlamydia are asymptomatic.

Several important complications may result from chlamydial infections, including pelvic inflammatory disease, ectopic pregnancy and tubal infertility in women, epididymo-orchitis in males, and conjunctivitis and reactive arthritis in both sexes. Transmission to neonates during delivery may lead to neonatal conjunctivitis and pneumonia.

• Chlamydia trachomatis is an intracellular organism, specimens must include epithelial cells and not exudates alone.

• Nucleic acid-based amplification tests (NAAT): most sensitive 90–95%, highly specific, new gold standard; polymerase chain reaction (PCR) can be used to test a range of specimens (urine, urethral, cervical, rectal, pharyngeal).

• Females - cervical or vulvo-vaginal swabs are specimens of choice, followed by first void urine (FVU); males - FVU is as sensitive as urethral swabs; care with inhibitors with urine specimens; storing urine overnight at 40C or freeze-thawing may enhance sensitivity of urine specimens.

• NAATs may be used for conjunctival, pharyngeal and rectal specimens, although currently unlicensed for these sites; rectal swabs should be obtained via proctoscopy.

• Medico legal cases – samples for NAAT should be taken from all the sites where penetration has occurred, a reactive NAAT result must be confirmed using a different NAAT.

• Antigen detection methods – Direct Florescent Antigen (DFA) sensitivity 50–90%; enzyme immunoassay (EIA) poor sensitivity 50–70%, specificity >95%, inexpensive, can be used for large numbers of specimens. FVU or urethral swabs can be used for males, endocervical swabs are preferred for women.

• Cell culture for chlamydia in McCoy cell monolayers, used to be the gold-standard, it is fairly sensitive (70–80%) and 100% specific, requires stringent cold-chain, costly, very expensive, not readily available anymore.

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• Giemsa-stained direct smear for the inclusion bodies within infected cells is useful only for ocular infections.

• Serological tests are not useful to diagnose acute chlamydial infections because of cross-reactivity between chlamydial species, high prevalence of chlamydia antibodies in high risk populations, and the unpredictability of serological response and changes in titres of IgM and IgG antibodies in acute uncomplicated infections. TREATMENT

Uncomplicated urethral, endocervical, pharyngeal or rectal infections in adults 1. Doxycycline 100 mg orally bid x 7 days [1a, A]

or

2. Azithromycin 1 g orally single dose [1a, A] Alternative regimens (A)

1. Erythromycin 500 mg orally qid [1b, A] or

2. Ofloxacin 200 mg orally bid or 400 mg orally od x 7 days [1b, A] or

3. Levofloxacin 500 mg orally od x 7 days [1b, A] or

4. Tetracycline HCl 500 mg orally qid x 7 days [1b, A] Not recommended

Ampicillin and Trimethoprim-Sulphamethoxazole Chlamydia trachomatis infection in pregnancy

Risk factors for Chlamydia trachomatis infection during pregnancy include young age (< 25 years), past history of other STIs, new sex partner within the last 3 months, and multiple sex partners. Pregnant women whose sexual partners have NGU should be examined, and screened for other STIs, and treated on epidemiological grounds.

1. Erythromycin 500 mg orally qid x 7 days [1a, A] or

2. Azithromycin 1 g orally single dose [1a, A] or

3. Amoxicillin 500 mg orally tid x 7 days [1a, A] Contra-Indicated

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Neonatal Chlamydia trachomatis conjunctivitis

The other differential diagnoses of conjunctivitis in infants are - gonococcal ophthalmia neonatorum, pyogenic and enteric Gram-negative conjunctivitis.

Diagnosis is made by culture or non-culture tests on specimens taken from the everted eyelid. Systemic treatment is essential to prevent complications such as chlamydia pneumonitis. Topical therapy alone is not adequate and unnecessary when systemic treatment is used. All neonates should be referred to an ophthalmologist.

Syrup Erythromycin - 50 mg/kg/day orally in 4 divided doses x 14 days

An association between oral erythromycin and infantile hypertrophic pyloric stenosis (IHIS) has been reported in infants aged <6 weeks who were treated with this drug. Infants treated with erythromycin should be followed for signs and symptoms of IHPS.

Mothers of infected infants and their sex partners should be screened and treated on epidemiological grounds. Follow up to determine resolution is recommended. The efficacy of erythromycin treatment is approximately 80%; a second course of therapy may be required. Chlamydia trachomatis pneumonia in infants

Characteristic signs include a repetitive staccato cough and hyperinflation and bilateral diffuse infiltrates on CXR. Wheezing is rare, and infants are often afebrile. Diagnosis is made by culture or non-culture tests on specimens taken from the nasopharynx or tracheal aspirates.

Syrup Erythromycin - 50 mg/kg/day orally in 4 divided doses x 14 days.

Mothers of infected infants and their sex partners should be screened and treated on epidemiological grounds. Follow up to determine resolution is recommended. The efficacy of erythromycin treatment is approximately 80%; a second course of therapy may be required. Chlamydia trachomatis pelvic inflammatory disease and epididymo-orchitis

1. Doxycycline 100 mg orally bid x 14 days [III, B] or

2. Ofloxacin 400 mg orally bid x 14 days [III, B] FOLLOW-UP

A test-of-cure is not necessary when treatment with a tetracycline or azithromycin has been completed, unless symptoms persist or reinfection is suspected.

Test-of-cure is however recommended after 4 weeks for infections in infants, children and pregnant women, or when erythromycin was used.

Non-culture tests (eg NAATs) done within 4 weeks of completing treatment may yield false positive tests due to persistence of chlamydial antigens.

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Owing to the increased risk of complications following repeat infection in females, rescreening for reinfection may be indicated especially for high-risk females after 3 to 4 months.

Serologic tests for Syphilis and HIV should be performed; if negative they should be repeated at 3 months for Syphilis and HIV, after the last risky exposure.

Sex partners of symptomatic male patients within the last 60 days (or the most recent sex partner if the last contact was > 60 days) should be screened and treated for chlamydial infection epidemiologically. The look-back period for contacts of female patients and asymptomatic males is longer e.g. 3 months.

References:

1. BASHH (2006). National Guideline for the Management of Genital Tract Infection with Chlamydia Trachomatis. Retrieved from http://www.bashh.org/documents/61/61.pdf 2. Johnson, R.E., Newhall, W.J., Papp, J.R., Knapp, J.S., Black, C.M., Gift, T.L., et al.

(2002). Screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections. (Vol 51, RR-15: 1 – 38). Retrieved from http://www.cdc.gov/std/labguidelines/ rr5115.pdf

3. Lau, C.Y., & Qureshi, A.K. (2002). Azithromycin versus Doxycycline for Genital Chlamydial Iinfections: A Meta-Analysis of Randomized Clinical Trials. PubMed, 29(9):497 – 502.

4. McMillan, I.R., Young, H., Ogilvie, M.M., & Scott. R.G. (2002). Clinical Practice in Sexually Transmissible Infections. London: Saunders Ltd.

5. MOH (2009). Management of Genital Ulcers and Discharges: Clinical Practice Guidelines. (Vol. 1). Singapore: Ministry of Health.

6. Workowski, K.A. & Berman, S. (2010). Sexually Transmitted Diseases Treatment Guidelines.(Vol. 59). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/ rr5912a1.htm

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GONORRHOEA

DEFINITION

Gonorrhoea is caused by the Gram-negative bacterium Neisseria gonorrhoeae. The common sites of infection include the urethra, the endocervix, the rectum, the pharynx and the conjunctiva.

Gonorrhoea is characterised clinically by a profuse purulent discharge from the affected genital site (> 80% in male urethritis, up to 50% in female cervicitis), often accompanied by local pain or discomfort. However asymptomatic infection occurs in 10% of urethral infection, >50% of cervical infection, >90% of pharyngeal and rectal infection. Contiguous spread of the infection can lead to epididymo-orchitis, prostatitis, endometritis and salpingo-oophritis. Haematogenous spread results in disseminated gonococcal infection (DGI).

• Presumptive diagnosis of gonorrhoea is made on finding Gram-negative intracellular diplococci in a smear of the discharge. In men, microscopy of urethral smears is more sensitive in symptomatic (90–95%) than in asymptomatic (50–75%) patients. In women sensitivity of microscopy of Gram-stained endocervical smears is around 50%. Microscopy is not appropriate for pharyngeal and rectal specimens.

• Confirmatory diagnosis is made by identification of the organism on selective culture media.

• NAATs (PCR) are more sensitive than culture and can be used as diagnostic/ screening tests on non-invasively collected specimens (urine and self-taken vaginal swabs). The sensitivity of NAATs is >90% for genital sites, whilst the sensitivity of culture may be < than 75% for endocervical swabs.

• There are currently no NAATs licensed for use with rectal or pharyngeal samples, although studies suggest that the sensitivity of NAATs at non-genital sites exceeds 90% whereas the sensitivity of culture can be <60% for rectal swabs and <50% for pharyngeal swabs.

• The DSC clinic currently uses NAATs to detect rectal, urethral and cervical GC, and cultures for pharyngeal GC.

• Some degree of caution is required in interpretation of positive results as the specificity of NAATs is not 100%; especially if the risk profile of the patient is at odds with the result. Confirmation of a NAAT positive result by culture can be considered in cases where there is some doubt. However, generally NAATs are considered reliable for detection.

• As nonculture tests cannot provide antimicrobial susceptibility results, in cases of persistent gonococcal infection after treatment, clinicians should perform both culture and antimicrobial susceptibility testing.

• Gonococcal complement fixation test (GC-CFT) should not be used for diagnosing gonorrhoea.

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Specimen collection: Males:

Routinely from the urethra; rectal and/or oropharyngeal tests when indicated by sexual activity. FVU provides an alternative urethral specimen for testing with a NAAT.

Females:

Routinely from endocervix if speculum examination performed; and rectal and oropharyngeal tests when indicated by the sexual history. Urine or a self-taken vaginal swab are suitable alternative specimens as screening tests using a NAAT.

TREATMENT

Uncomplicated infection in adults - urethral, endocervical and rectal infection

1. Ceftriaxone 500 mg i/m single dose + azithromycin 1-2g stat or doxycycline 100 bid x 1-2 weeks [IV, C]

Alternative Regimens (for those with allergy)

1. Cefotaxime 1g i/m single dose + azithromycin 1-2g stat or doxycycline 100 bid x 1-2 weeks [1b]

or

2. Spectinomycin 2g i/m single dose + azithromycin 1-2g stat or doxycycline 100 bid x 1-2 weeks [1b, A]

or

3. Azithromycin 2g stat [II, C] (not as monotherapy) or

4. Aztreonam 1g i/m single-dose dose with azithromycin 1-2g stat or doxycycline 100 bid x 1-2 weeks [1b]

(Aztreonam has been used in some patients at DSC when other alternatives were unavailable)

It is important to emphasize that treatment of GC should be accompanied with anti-chlamydia therapy. This not only treats concurrent infection, but there is evidence to suggest that concurrent administration of azithromycin would slow down the possibility of the development of cephalosporin resistant strains of GC.

Note: The fluroquinolones (e.g. ciprofloxacin, ofloxacin, norfloxacin) are contraindicated as > 70% of isolates in Singapore and the region are resistant.

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Gonococcal infection in pregnancy

• Cephalosporins [IV, C] in the recommended dosages are safe and effective in pregnancy.

• Spectinomycin [Ib, A] can be administered to women who are unable to tolerate cephalosporins.

• Simultaneous treatment for chlamydial infection with azithromycin 1g stat or erythromycin 500 mg orally qid x 7 – 14 days is advocated.

Pharyngeal infection

1. Ceftriaxone 500 mg i/m single dose with azithromycin 1g stat or doxycycline 100 bid x 1 week [IV, C].

Disseminated gonococcal infection or DGI Hospitalisation under specialist care is recommended. 1. Ceftriaxone 1g i/m or i/v daily

or

2. Cefotaxime 1g i/v 8 hourly or

3. Spectinomycin 2 g i/m 12 hourly

Therapy should continue for 24-48 hours after improvement begins, and can be converted to an oral cephalosporin therapy for a total of 7 days. Anti-chlamydia therapy should be given at the same time.

Gonococcal acute epididymitis and epididymo-orchitis

Ceftriaxone 500 mg i/m daily x 1 to 3 days with doxycycline 100mg bid x 2 weeks [III, B]. Adult gonococcal ophthalmia

Ceftriaxone 1g i/m single dose with with azithromycin 1g stat or doxycycline 100 bid x 1 week. With lavage of the infected eye with normal saline [IV, C].

Topical antibiotics alone do not eradicate the infection and rigid adherence to topical therapy is not essential. All patients should be referred for ophthalmologic assessment.

Neonatal gonococcal ophthalmia

1. Ceftriaxone 25-50 mg/kg i/m single dose not to exceed 125 mg or

2. Cefotaxime 100 mg/kg i/m single dose. With lavage of the infected eye with normal saline.

Topical antibiotics alone do not eradicate the infection. All patients should be referred for ophthalmologic assessment.

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Screen the mother and her sexual partners for gonorrhoea and other STIs. The mother should be treated on epidemiological grounds.

Uncomplicated gonococcal infections in older children - urethral, vulvovaginal, cervical, pharyngeal, rectal infections.

Children who weigh > 45 kg or are above 12 years of age should be treated with adult regimens.

Children who weigh < 45 kg or are 12 years of age or younger should be treated as follows: 1. Ceftriaxone 125 mg i/m single dose with azithromycin 1g stat or doxycycline 100 bid x 1

week (if older than 12 years). or

2. Cefotaxime 125 mg i/m single dose with azithromycin 1g stat or doxycycline 100 bid x 1 week (if older than 12 years).

Drugs Not Recommended

The following drugs are not recommended for treating gonococcal infection in Singapore as they are either ineffective or have not been adequately evaluated:

• All tetracyclines (they are given as part of anti-chlamydia therapy, not as primary treatment for GC) • All penicillins • All fluoroquinolones • Erythromycin • Rifampicin • Kanamycin • Trimethoprim/sulfamethoxazole FOLLOW-UP

• Test-of-cure is recommended in all cases, in particular for pharyngeal GC.

• All treatments are less effective at eradicating pharyngeal infection and test-of-cure is recommended following treatment of infection at this site.

• In the DSC Clinic test-of-cure and assessment for post-gonococcal urethritis (PGU) is performed after 14 days.

• Test-of-cure is done using urethral smear. In cases of possible antibiotics resistance, cultures should be performed.

• Patients with gonococcal ophthalmia should have cultures done daily while on therapy and again on the 5th and 14th days after completion of therapy.

• Serologic tests for syphilis and HIV should be performed; if negative they should be repeated at 3 months after the last risky exposure.

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Sexual contacts of the patients in the preceding 60 days should be traced, screened and treated on epidemiologic grounds. If the last sexual exposure was > 60 days, the patient’s most recent partner should be treated.

References:

1. Bignell, C., & FitzGerald, M. (2011). National Guideline on the Diagnosis and Treatment of Gonorrhoea in Adults. Retrieved from http://www.bashh.org/ documents/3611

2. Workowski, K. & Berman, S. (2010). CDC Sexually Transmitted Disease Treatment Guidelines (2010). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/ rr5912a1.htm

3. McMillan, I.R., Young, H., Ogilvie, M.M., & Scott. R.G. (2002). Clinical Practice in Sexually Transmissible Infections. London: Saunders Ltd.

4. Cook, R.L., Hutchison, S.L., Østergaard, L., Braithwaite, R.S., & Ness, R.B. (2005). Systematic Review: Non-invasive Testing for Chlamydia Trachomatis and Neisseria Gonorrhoea. Ann Intern Med, 142: 914-925. Retrieved from PubMed.

5. Tapsall, J.W, Ndowa, F., Lewis, D.A., & Unemo, M. (2009). Meeting the Public Health Challenges of Multi and Extensively-Drug Resistant Neisseria gonorrhoea. Expert Rev Anti Infect Ther, 7:821-34. Retrieved from PubMed.

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GRANULOMA INGUINALE (DONOVANOSIS)

DEFINITION

It is a sexually transmitted infection caused by the gram-negative bacillus Klebsiella granulomatis (formerly known as Calymmatobacterium granulomatis). This infection is rarely seen locally but endemic in India, parts of South America and southern Africa.

Presents with painless “beefy” red (highly vascular) granulomatous genital ulcers which bleed easily; without regional lymphadenopathy. Other clinical presentations are - nodular, hypertrophic, necrotic, and sclerotic types. The lesions may develop secondary bacterial infection or may be co-infected with another STI.

• Tissue smears from ulcer to reveal intra-cellular Donovan bodies (Giemsa, Wright’s or silver stains) with “safety-pin” bipolar staining, found within histiocytes

• Biopsy of the ulcer to reveal granulomas and Donovan bodies

• Donovan bodies are characterised by :

i. Location within large (20-90 μm) histiocytes, ii. Pleomorphic appearance 1- 2 x 0.5-0.7 μm iii. Bipolar densities and a capsule often visible iv. Stain Gram negative

• Culture is difficult

• There are currently no FDA approved PCR kits for diagnosis TREATMENT

LOCAL TREATMENT Normal saline wash SYSTEMIC TREATMENT Recommended regimens

1. Doxycycline 100 mg orally bid x minimum of 3 weeks [IV, C] or

2. Azithromycin 1 g orally once a week for 4 to 6 weeks [lb, B] Alternative regimens

1. Erythromycin 500 mg orally qid x minimum of 3 weeks [IV, C] or

2. Co-trimoxazole (trimethoprin/sulfamethoxazole) 160/800 mg orally (2 tabs) bid x minimum of 3 weeks [Ilb, B]

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3. Gentamicin 1 mg/kg i/m tid as adjunct to above agents if not responding [lll, C] or

4. Ciprofloxacin: 750 mg orally bid x minimum of 3 weeks [llb, B] FOLLOW-UP

If the treatment is effective, clinical response is evident within 7 days. Treatment should be continued till ulcers heal completely. Relapse can occur 6-18 months after apparently effective therapy.

Management of Sex Partners

Persons who have had sexual contact with a patient who has granuloma inguinale within 60 days before onset of the patient’s symptoms should be examined and offered therapy. However, the value of empiric therapy in the absence of clinical signs and symptoms has not been established.

Special Considerations Pregnancy

Pregnancy is a relative contraindication to the use of sulfonamides. Pregnant and lactating women should be treated with erythromycin, and consideration should be given to the addition of a parenteral aminoglycoside (e.g. gentamicin). Azithromycin may be useful for treating granuloma inguinale in pregnancy. Doxycycline and ciprofloxacin are contraindicated in pregnant women.

HIV Infection

Persons with both granuloma inguinale and HIV infection should receive the same regimens as those who are HIV negative. Consideration should be given to the addition of a parenteral aminoglycoside (e.g. gentamicin).

References:

1. Workowski, K. & Berman, S. (2010). CDC Sexually Transmitted Disease Treatment Guidelines (2010). Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/ rr5912a1.htm

2. BASH. (2011). United Kingdom National Guideline for the Management of Donovanosis (Granuloma Inguinale). Retrieved from http://www.bashh.org/ documents/3194

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HEPATITIS A VIRUS INFECTION

DEFINITION

Hepatitis A (HAV) is a picorna (RNA) virus. Transmission occurs via faeco-oral (via food, water, close personal contact) route. Outbreaks have been reported in MSM, linked to oro-anal or digital rectal contact. Outbreaks have also been reported amongst intravenous drug users, in institutions for people with learning difficulties, and in contaminated batches of factor VIII.

Patients are infectious for approximately 2 weeks before and 1 week after the jaundice by the non-parenteral routes but virus can be found in the blood and stool until after the serum amino transferase levels have peaked. In HIV positive patients, HAV viraemia may continue for over 90 days.

In 2010 there were 68 serologically confirmed HAV infections in Singapore. CLINICAL FEATURES

Incubation Period: 15-45 days.

Most children and up to half of adults are asymptomatic or have mild non-specific symptoms with little or no jaundice.

In the more ‘typical’ case there are 2 phases of symptoms

• The prodromal illness: flu-like symptoms (malaise, myalgia, fatigue), often with right upper abdominal pain. This phase lasts for 3-10 days.

• This is followed by the icteric illness: jaundice (hepatic and cholestatic) associated with anorexia, nausea, fatigue, liver enlargement and tenderness. Usually lasts for 1- 3 weeks. It can persist for 12 or more weeks in a minority of patients who have cholestatic symptoms (itching and deep jaundice).

Fulminant hepatitis complicates approximately 0.4% of cases, more common in patients already infected with chronic hepatitis B or C. Chronic infection (>6 months) has only been reported in a very small number of case-reports; overall mortality is < 0.1%.

DIAGNOSIS

Confirmed by a positive serum Hepatitis A virus specific IgM (HAV-IgM) which remains positive for six months or more.

HAV-IgG does not distinguish between current or past infection and may remain positive for life. Antibody produced in response to HAV infection persists for life and confers protection against reinfection.

Other tests:

• Serum amino-transferases (AST/ALT)

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Serum alkaline phosphatase (SAP) will usually be < 2x the upper limit of normal, but higher if there is cholestasis. Prothrombin time PT prolongation by >5 seconds suggests developing hepatic decompensation.

MANAGEMENT

Patients should be advised to avoid food handling and unprotected sexual intercourse until they have become non-infectious.

Hepatitis A is a notifiable disease.

Screen for other STIs in cases of sexually-acquired hepatitis or if otherwise appropriate. Mild / moderate icteric hepatitis (80%) - manage as an outpatient emphasising rest and oral hydration [III, B].

Severe icteric hepatitis with vomiting, dehydration or signs of hepatic decompensation (change in conscious level or personality) - admit to hospital [III, B].

SEXUAL AND OTHER CONTACTS

Partner notification should be performed for at-risk homosexual contacts (oral/anal, digital/ rectal and penetrative anal sex) within the period 2 weeks before to 1 week after the onset of jaundice.

Hepatitis A vaccine may be given up to 7 days after exposure providing exposure was within the infectious period of the source case (during the prodromal illness or first week of jaundice) [IIa, B].

Hepatitis A vaccine schedule: doses at 0 and 6-12 months, 95% protection for at least 5 years [Ib, A].

Current advice is to revaccinate after 10 years [IIb, B], however there is increasing evidence that vaccine-induced immunity may be > 20 years and possibly lifelong, so no further booster doses may be needed after the primary course in immunocompetent patients.

HIV positive patients respond in 46-88% but titres are lower than in HIV negative individuals, and correlates with CD4 count [IIa, B].

A combined Hepatitis A+B vaccine given on the same schedule as the hepatitis B vaccine has similar efficacy to the individual vaccines although early immunity to hepatitis B may be impaired [IIa, B].

PRIMARY PREVENTION

Most MSM are not at increased risk for hepatitis A infection and therefore universal vaccination in this group cannot be firmly recommended [III, B]. However, many outbreaks have been reported amongst homosexual men in large cities and therefore clinics in these areas should offer vaccination, particularly when increased rates of infection have been recognised locally [III, B].

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Screening for pre-existing hepatitis A exposure before vaccination has been found to be cost effective [III,B].

Intravenous drug users and patients with chronic hepatitis C infection should be vaccinated [III, B]. Vaccination is also recommended for travellers to developing countries, people with haemophilia or chronic liver disease, those with occupational exposure and for people at risk in an outbreak [Ib, A]. Postvaccination serologic testing is not indicated because most persons respond to the vaccine.

HEPATITIS B VIRUS (HBV)

DEFINITIONS

Hepatitis B virus (HBV) is a DNA Hepadna virus that causes an infection of the liver. Transmission is through blood or body fluids viz. mother-to-child transmission, sexual intercourse, transfusion of contaminated blood, and sharing of needles and syringes. Sporadic infection occurs in people without apparent risk factors, in institutions for learning difficulties and also in children in countries of high endemicity, but in these cases the means of transmission is poorly understood.

A total of 65 cases of acute hepatitis B infections were reported in 2010. The overall age-standardised prevalence of HBsAg among Singapore residents aged 18 to 69 years decreased significantly from 4.0% in HBSS 1999 to 2.8% in HBSS 2005 (p = 0.002). CLINICAL FEATURES

Incubation period. 40-160 days Symptoms

• Virtually all infants and children have asymptomatic acute infection

Asymptomatic infection is also found in 10-50% of adults in the acute phase and is especially likely in those with HIV coinfection

• Chronic carriers are usually asymptomatic but may have fatigue or loss of appetite

• The prodromal and icteric phases are very similar to hepatitis A, but may be more severe and prolonged

Signs

• As for Hepatitis A in the acute phase

• If chronic infection occurs there are often no physical signs. After many years of infection, depending on the severity and duration, there may be signs of chronic liver disease

Complications

• Fulminant hepatitis occurs in <1% of symptomatic cases but carries a worse prognosis than that caused by hepatitis A

• Chronic infection (>6 months) occurs in 5-10% of symptomatic cases but the rate is higher in immunocompromised patients with HIV infection, chronic renal failure or those receiving immunosuppressive drugs. Immunosuppressive treatment can also

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reactivate hepatitis B. Almost all (>90%) of infants born to infectious (HBeAg +ve) mothers will become chronic carriers unless immunised

• There are 4 phases of chronic carriage:

1. Immune Tolerant (HBe Ag +ve, normal ALT levels, little or no necroinflammation on liver biopsy)

2. Immune Active, HBe Ag +ve phase (HBe Ag +ve, raised ALT, progressive necroinflammation and fibrosis)

3. Inactive hepatitis B carrier (HBsAg+ve, HBeAg -ve, low levels of HBV DNA and normal ALT)

4. HBeAg –ve chronic active hepatitis (Precore, Corepromotor mutations, HBeAg –ve, detectable HBV DNA, progressive inflammation and fibrosis). Types 2 and 4 may progress to cirrhosis and liver cancer, with type 4 generally progressing fastest

• Concurrent hepatitis C infection can lead to fulminant hepatitis, more aggressive chronic hepatitis and increased risk of liver cancer. Concurrent HIV infection increases the risk of progression to cirrhosis and death. Hepatitis A coinfection can be severe acutely, but may lead to the reduction of longterm HBV replication

• Concurrent Delta virus infection, or delta virus superinfection may lead to progressive fibrosis, cirrhosis and endstage liver disease

• Mortality is <1% for acute cases. Between 10 – 50 % of chronic carriers will develop cirrhosis leading to premature death in approximately 50%. Ten percent or more of cirrhotic patients will progress to liver cancer

• There is an increased rate of miscarriage/premature labour in acute infection. There is a risk of vertical transmission

LABORATORY TESTS Serologic markers

The order of appearance of markers in acute infections is - HBsAg, HBeAg, antiHBc IgM, antiHBe, antiHBc IgG, antiHBs (Annex VI).

The significance of HBs antigen and antibody markers is shown below:

Marker Clinical Significance

HBsAg Presence of HBV

HBeAg Virus replication, High infectivity

Anti-HBc IgM Acute infection

Anti-HBc IgG Late acute or chronic infection Anti-HBe Loss of replication, low infectivity

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TREATMENT

Patients should be advised to avoid unprotected sexual intercourse until they have become non-infectious or their partners have been successfully vaccinated [III,B]. Hepatitis B is a notifiable disease. Screen for other STIs in cases thought to have been sexually acquired or if otherwise appropriate.

General counselling:

• No donation of blood, sperm, milk, organs

• No sharing of toothbrushes, shavers

• Household contacts, sexual partners to be immunized if negative HBsAg, anti-HBs and anti-HBc

• Pregnant carrier – inform O&G

• Healthy diet, avoid regular alcohol

• Steroids and immunosuppressive agents can aggravate latent infection

• Clean blood spills with bleach/detergents Note:

Hepatitis B virus transmission is not transmissible through:

• Sharing of utensils, food or kissing as part of social greetings

• Participating in all activities including contact sports and social interaction with others (e.g. in schools, day care centres) [IV, D]

Acute Hepatitis - as for hepatitis A. Chronic Hepatitis B Infection

Management of patients with chronic hepatitis B should be tailored according to the clinical state of liver disease (compensated versus decompensated liver disease) as well as virologic and biochemical (i.e. the liver function test, in particular the serum transaminase levels) status.

1) For patients with HBsAg positive > 6 months and well compensated liver disease: a. HBeAg–positive hepatitis B virus infection and:

i. ALT < Upper limit of normal (ULN): no pharmacotherapy needed. Monitor ALT at least 6 monthly and HBeAg at least 12 monthly

ii. ALT 1-2 X ULN: monitor ALT 3 to 6 monthly and HBeAg 6 monthly. Refer to specialist if persistent evidence of early deterioration of liver function or age >40. Consider liver biopsy and treatment if biopsy shows significant liver damage

iii. ALT > 2X ULN: repeat ALT and HBeAg within 1 to 3 months. Refer to specialist if persistent. Treat immediately upon evidence of hepatic decompensation b. HBeAg–negative hepatitis B virus infection and:

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i. ALT < ULN: Monitor ALT 3 months later. If still normal, monitor ALT every 6 to 12 monthly

ii. ALT 1-2X ULN: Monitor ALT 3 to 6 monthly. Refer to specialist if persistent, evidence of early deterioration of liver function or age > 40. If HBV DNA is > 2000 IU/ml, consider liver biopsy and treat if biopsy shows significant liver damage

iii. ALT > 2X ULN: repeat ALT within 1 to 3 months. Refer to specialist if persistent. If HBV DNA > 2000 IU/ml, consider treatment if persistent. Note that common conditions, such as fatty liver and commonly consumed drugs may be confounding factors giving rise to mild to moderate elevation of serum transaminases

2) For patients with decompensated hepatitis B virus–related cirrhosis: Refer to gastroenterologist or hepatologist for management [IV, D].

Surveillance of patients with chronic hepatitis B should be carried out regularly; frequency of surveillance will depend on the risk profile, which should be determined before the start of the surveillance programme (see below):

a. Baseline assessment to stratify risk

i. check serum ALT, AST, bilirubin, albumin, prothrombin time, alpha-fetoprotein, HBsAg, HBeAg, anti HBe and HBV DNA

ii. liver imaging

b. Periodic reassessment is necessary

Frequency of surveillance is dependent on patients’ risk profile:

i. Low-risk group (patients who have seroconverted and have a nonreplicative hepatitis B virus infection): 6 monthly serum ALT and bilirubin – if abnormal, HBV DNA should be checked

ii. Medium-risk group (patients with replicative HBV infection who are beyond the immuno-tolerant window; chronic hepatitis B not on treatment; chronic hepatitis B which is resistant to treatment; patients who are expected to tolerate exacerbation of hepatitis B poorly, e.g. patients with liver cirrhosis): 4-6 monthly serum ALT and bilirubin assessment – if abnormal, HBV DNA should be checked

iii. High-risk group (patients who are subjected to immunosuppressive treatment either during immunosuppressive treatment or on withdrawal of immunosuppressive treatment with agents such as steroids, cytotoxics, monoclonal antibodies with imunomodulatory activity; patients withdrawn from nucleoside/tide analogue treatment for prior chronic hepatitis B; demonstrating resistance to their ongoing nucleoside/tide analogue treatment for their prior chronic hepatitis B; having reduced liver mass, e.g. post-hepatic resection): 2-4 monthly serum ALT, bilirubin, HBV DNA, appropriate to each set of circumstances. If abnormal the specialist will have to decide on further appropriate management [GPP]

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Most patients in medium risk group and all patients in high risk group should be referred for management by a specialist.

Treatment of Chronic Hepatitis B Infection

• Treatment should normally be given in collaboration with a hepatologist or physician experienced in the management of liver disease [IV, C]. The decision to treat depends on pattern of disease, HBV DNA level, and presence or absence of significant necroinflammation and hepatic fibrosis. A HBV DNA level of ≥ 4 log IU/ml is generally considered as significant and treatment should be considered

• Patients should be considered for therapy with lamivudine, adefovir, tenofovir, telbivudine, entecavir (or combinations of nucleos(t)ide analogues) or pegylated interferon [Ib, A]. Additional treatments that may soon be licensed in HBV monoinfection include emtricitabine (FTC) [Ib,A], clevudine [II,B] and valtorcitabine [III,C]. Treatment responders have long term benefits in terms of reduced liver damage and decreased risk of liver cancer

• All patients should have an HIV test prior to starting HBV therapy because of different treatment strategies required and the significant risk of antiretroviral resistant HIV developing if lamivudine, tenofovir or entecavir are used as monotherapy [Ib,A]

• Lamivudine, emtricitabine and tenofovir will suppress hepatitis B viral replication during therapy of HIV, and may delay liver damage if given as part of triple antiretroviral therapy [Ib, A]

• Lamivudine and emtricitabine should only be given to HIV+ patients in combination with tenofovir as part of HAART because of the rapid high rate of resistance that occurs to these drugs if given as the only HBV active agent [Ib,A]

• Entecavir should not be used in HIV+ patients without adequately suppressed HIV as it causes the M184V (lamivudine/emtricitabine) resistant mutation

• Adefovir or telbivudine can be used alone in HIV+ patients [II,B]

• Active surveillance of cirrhotic patients for Hepatocellular carcinoma (HCC) leads to earlier detection and better treatment outcomes

Pregnancy and Breastfeeding

• Vertical transmission of infection occurs in 90% of pregnancies where the mother is HBeAg +ve and in about 10% of HBsAg +ve, HBeAg -ve mothers. More than 90% of infected infants become chronic carriers

• Infants born to infectious mothers are vaccinated from birth, usually in combination with Hepatitis B specific Immunoglobulin 200 i.u. i.m. [Ia, A]. This reduces vertical transmission by 90%

• There is some evidence that treating the mother in the last month of pregnancy with lamivudine may further reduce the transmission rate if she is highly infectious [III, C], but this needs to be further substantiated

• Infected mothers should continue to breast feed as there is no additional risk of transmission [II, B]

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SEXUAL AND OTHER CONTACTS

Partner notification should be performed and documented and the outcome documented at subsequent follow-up. Contact tracing to include any sexual contact or needle sharing partners during the period in which the index case is thought to have been infectious. The infectious period is from 2 weeks before the onset of jaundice until the patient becomes surface antigen negative. In cases of chronic infection trace contacts as far back as any episode of jaundice or to the time when the infection is thought to have been acquired, this may be impractical for periods of longer than 2 or 3 years.

SCREENING AND PRIMARY PREVENTION

Hepatitis B testing in asymptomatic patients should be considered in MSM, sex workers, injecting drug users, HIV-positive patients, sexual assault victims, needle-stick victims and sexual partners of positive or high-risk patients. If non-immune, consider vaccination. If found to be chronic carriers consider referral for therapy.

With the exception of newborns, serological screening provides a basis for vaccination of an individual without giving an infected individual a false sense of security. Prophylactic vaccination is of no benefit to an individual who already has chronic hepatitis B virus infection; he/she should instead be followed up regularly and treated when indicated. Serological screening for HBsAg and Ab should be done within 6 months pre-vaccination for all except newborn babies [IV, D].

Sexually. Management Guidelines Published by

Sexually

TranSmiTTed

infecTionS

management Guidelines

2013

Published by

DSC CLINIC

NATIONAL SKIN CENTRE

© 2013

CONTENTS

PREFACE

PRINCIPLES OF STI MANAGEMENT

BACTERIAL VAGINOSIS

CANDIDIASIS

CHANCROID

CHLAMYDIA TRACHOMATIS INFECTIONS

GONORRHOEA

GRANULOMA INGUINALE (DONOVANOSIS)

HEPATITIS A VIRUS INFECTION

HEPATITIS B VIRUS (HBV)